Interferon-gamma is involved in photoimmunoprotection by UVA (320-400 nm) radiation in mice

Ultraviolet B radiation not only inflicts tumor-initiating DNA damage, but also impairs T cell-mediated immunity relevant to survival of the initiated cells. We have reported, however, that ultraviolet A radiation, in contrast, is immunologically innocuous in hairless mice and opossums, but renders the animals resistant to the immunosuppression by ultraviolet B, or its mediator cis-urocanic acid. Ultraviolet B irradiation of skin causes abundant release of numerous cytokines (interleukin-1, interleukin-6, interleukin-10, tumor necrosis factor-alpha); notably interleukin-12 and interferon-gamma do not appear to be upregulated. A recent report has indicated that interleukin-12 protects from photoimmunosuppression in mice, but it remains unclear whether interleukin-12 acts directly or via interferon-gamma, which it is known to stimulate. Here we investigate the possible role of interferon-gamma in UVA photoimmunoprotection, using interferon-gamma gene knockout mice in comparison with control C57/BL6 mice, and the systemic contact hypersensitivity reaction (induced by sensitization through a nonirradiated skin site) to measure immunity. interferon-gamma-/- mice raised normal contact hypersensitivity responses, and were unaffected, as were C57BL control mice, by ultraviolet A exposure. In response to ultraviolet B irradiation or topical cis-urocanic acid treatment, control mice became immunosuppressed by 69% and 27%, respectively, and interferon-gamma-/- mice by 79% and 27%. When ultraviolet B exposure or cis-urocanic acid was followed by ultraviolet A irradiation, however, contact hypersensitivity was totally restored in control mice, but remained suppressed by 55% and 25%, respectively, in interferon-gamma-/- mice. Injection of recombinant interferon-gamma in the interferon-gamma-/- mice restored the ultraviolet A protective effect against cis-urocanic acid-induced immunosuppression. These observations suggest that interferon-gamma plays a part in ultraviolet A immunoprotection from the suppressive effect of ultraviolet B radiation and, and that the mechanism appears to be via antagonism by this cytokine of the cis-urocanic acid immunosuppressive action.